S1PR1, also known as S1P1 and Edg-1, is a widely expressed G-protein–coupled receptor for sphingosine-1-phosphate (S1P), a bioactive lipid found in the bloodstream. Activation of S1PR1 inhibits angiogenic sprouting and enhances cell-to-cell adhesion by regulating VE-cadherin at endothelial junctions during embryogenesis. Consequently, S1PR1 signalling plays a crucial role in vascular development and stability (1).
In adult vertebrates, S1PR1 regulates diverse physiological processes, including vascular and lymphatic permeability, astrocyte proliferation, neuronal protection, lymphocyte egress, marginal B-cell migration in secondary lymphoid organs, heart rate regulation, endothelial integrity, and responses to ischemia-reperfusion injury in multiple tissues (2,3).
S1PR1 is expressed in astrocytes and endothelial cells in the brain, where it is linked to reactive astrocytes and neuroinflammation. Recent findings show that neuronal contact induces S1PR1 expression in perisynaptic astrocyte processes, promoting astrocyte morphology, morphogenesis, and the release of synaptogenic factors crucial for neural circuit formation (4,5).